1 Field of the Invention
The present invention relates to extended release pharmaceutical formulations, preferably in the form of particles which are used in a tablet, capsule, or particulate form, for slowly releasing medicament over periods of time of from 12 to at least 24 hours. The extended release pharmaceutical formulations can contain both an immediate release formulation, as well as a extended release formulation, or simply the extended release formulation. The invention also relates to a method for preparing the extended release formulation and its administration to mammals.
2 Description of Related Art
It is of significant advantage to both the patient and clinician that medication be formulated so that it may be administered in a minimum number of daily doses from which the drug is uniformly released over a desired, extended period of time. Various techniques have been developed for the purpose of including a pharmaceutical preparation comprising a drug-containing particle with a coating layer and a pharmaceutical preparation comprising a continuous matrix with a drug dispersed therein, such as embedded into a rigid lattice of resinous material. In these pharmaceutical preparations, the coating layer or matrix comprises a substance insoluble, or hardly soluble, in aqueous body fluids, and the release of the drug is controlled by means of the resistance of said coating layer or matrix against the diffusion of the drug therethrough. Such pharmaceutical preparations are characterized in that the particles used in making the matrix, are made as hardly disintegratable as possible. The release of the drug from such pharmaceutical preparations is driven by the gradient of the drug concentration resulting from penetration of water by diffusion into the formulation. In this mode of release, at the latter stage of release, the rate of the release is described by Fick's law, that is, the rate of release decreases due to the decrease in the concentration gradient and the increase in the distance of the diffusion.
U.S. Pat. No. 3,458,622 to HILL discloses a controlled release tablet for the administration of medicinal agents over a prolonged period of up to about 8 hours. This patent discloses a compressed tablet for the prolonged release of a medicament containing that medicament in a core formed from a polymeric vinyl pyrrolidone, preferably polyvinyl pyrrolidone (PVP), and a carboxyvinyl hydrophilic polymer (hydrocolloid). The core material formed from the two polymeric substances provides the controlled release effect by forming a complex under the action of water or gastric fluid.
U.S. Pat. No. 4,252,786 to WEISS et al. applies a rupturable, relatively water-insoluble, water-permeable film formed of a combination of hydrophobic and hydrophilic polymers over an insoluble swelling type delayed release matrix or core containing the medicament which core includes a blend of polyvinyl pyrrolidone and a carboxyvinyl hydrophilic polymer.
U.S. Pat. No.4,140,755 to SHETH et al. discloses a sustained release formulation in the form of sustained release tablets which contain a homogeneous mixture of one or more medicaments with one or more hydrophilic hydrocolloids, such as hydroxypropylmethylcellulose having a viscosity of 4000 cps. The hydrocolloids when contacted with gastric fluid at body temperatures form a sustained gelatinous mix on the surface of the tablet causing the tablet to enlarge and acquire a bulk density of less than 1. The medicament is slowly released from the surface of the gelatinous mix which remains buoyant in the gastric fluid.
U.S. Pat. Nos. 4,309,404 and 4,248,857 to DeNEALE et al., disclose slow release formulations formed of a core material containing the active drug (31-53%), carboxypolymethylene (7-14.5%), zinc oxide (0-3%), stearic acid (4.5-10%), and mannitol (3-30%); a seal coating surrounding the core; and a sugar coating surrounding the seal coating.
U.S. Pat. No.4,309,405 to GULEY et al. discloses a sustained release tablet similar to that disclosed in DeNEALE et al. (4,304,404) except that the core contains 20 to 70% drug, 30 to 72% of a mixture of a water-soluble polymer such as hydroxypropylmethylcellulose or hydroxypropylcellulose and water-insoluble polymer (ethylcellulose alone or in admixture with carboxypolymethylene, hydroxypropylcellulose and the like).
Each of the DeNEALE et al. and GULEY et al. patents disclose that their compositions provide substantially zero order release of the core contained drug for about 12 hours following the first hour of administration. Thus, zero order release is only obtained after the initial surge of release of drug in the first hour.
U.S. Pat. No. 4,259,314 to LOWEY discloses a controlled long-acting dry pharmaceutical composition which includes a dry carrier formed from a mixture of hydroxypropylmethylcellulose (viscosity of 50 to 4000 cp in 2% aqueous solution at 20.degree. C.) and hydroxypropylcellulose (viscosity of 4000 to 6500 cp for a 2% aqueous solution at 25.degree. C.) which dry carrier is employed with a therapeutic agent such as aspirin, ascorbic acid and nitroglycerin.
U.S. Pat. No. 4,610,870 to JAIN et al. discloses a controlled release pharmaceutical formulation which approaches zero order release of active drug, which is provided preferably in the form of a coated tablet, containing a core portion from which medicament, such as procainamide hydrochloride, is slowly released over a controlled length of time. The core also includes one or more hydrocolloid gelling agents having a viscosity of within the range of from about 10,000 to about 200,000 centipoises in 2% solution at 20.degree. C., such as hydroxypropylmethylcellulose and/or . methylcellulose, one or more non-swellable binders and/or wax binders (where the medicament and/or hydrocolloid gelling agents are non-compressible), one or more inert fillers or excipients, one or more lubricants, and optionally one or more antiadherents such as dioxide and water.
Enteric-coated preparations are also referred to as another type of sustained release preparation. The release of the drug from an enteric-coated preparation is delayed by providing a coating layer soluble only after arrival at the intestine, that is after the pharmaceutical preparation passes through the stomach, and the extent of this delay is determined by the rate at which the pharmaceutical preparation is generally discharged from the stomach into the intestine. By combining an enteric portion with a usable portion soluble in the stomach, the release of the drug can be rendered continuously.
U.S. Pat. No. 4,695,467 to UEMURA et al relates to a sustained release tablet which comprises easily disintegrable granules containing (a) a drug, (b) a disintegrating agent selected from the group consisting of starch derivatives, gums, cellulose derivatives and ion- exchange resins, and (c) a water-soluble polymer selected from the group consisting of cellulose derivatives, synthetic water soluble polymers and polysaccharides, the surfaces of which granules are treated with a wax selected from the group consisting of plant or animal wax, hydrogenated oils and paraffin.